Digital Commons Network^™

Histone H3.3 Beyond Cancer: Germline Mutations In Histone 3 Family 3a And 3b Cause A Previously Unidentified Neurodegenerative Disorder In 46 Patients, Laura Bryant, Marcia C Willing, Linda Manwaring, Et Al

Open Access Publications

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (

A Matricellular Protein Fibulin-4 Is Essential For The Activation Of Lysyl Oxidase, Kazuo Noda, Kaori Kitagawa, Takao Miki, Masahito Horiguchi, Tomoya O Akama, Takako Taniguchi, Hisaaki Taniguchi, Kazuaki Takahashi, Yasumitsu Ogra, Robert P Mecham, Masahiko Terajima, Mitsuo Yamauchi, Tomoyuki Nakamura

Open Access Publications

Fibulin-4 is a matricellular protein required for extracellular matrix (ECM) assembly. Mice deficient in fibulin-4 (

Distinct Inflammatory Profiles Distinguish Covid-19 From Influenza With Limited Contributions From Cytokine Storm, Philip A Mudd, Jackson S Turner, Daniel Reynolds, Diane Bender, Adrianus C M Boon, Stacey L House, Kenneth E Remy, Richard S Hotchkiss, Rachel M Presti, Jane A O'Halloran, William G Powderly, Ali H Ellebedy, Et Al

Open Access Publications

We pursued a study of immune responses in coronavirus disease 2019 (COVID-19) and influenza patients. Compared to patients with influenza, patients with COVID-19 exhibited largely equivalent lymphocyte counts, fewer monocytes, and lower surface human leukocyte antigen (HLA)-class II expression on selected monocyte populations. Furthermore, decreased HLA-DR on intermediate monocytes predicted severe COVID-19 disease. In contrast to prevailing assumptions, very few (7 of 168) patients with COVID-19 exhibited cytokine profiles indicative of cytokine storm syndrome. After controlling for multiple factors including age and sample time point, patients with COVID-19 exhibited lower cytokine levels than patients with influenza. Up-regulation of IL-6, G-CSF, …

Adolescent Alcohol, Nuts, And Fiber: Combined Effects On Benign Breast Disease Risk In Young Women, Catherine S. Berkey, Rulla M. Tamimi, Walter C. Willett, Bernard Rosner, Martha Hickey, Adetunji T. Toriola, A. Lindsay Frazier, Graham A. Colditz

Open Access Publications

No abstract provided.

Natural Bladder Flling Alters Resting Brain Function At Multiple Spatial Scales: A Proof‑Of‑Concept Mapp Network Neuroimaging Study, Ishtiaq Mawla, Henry Lai, Gerald Andriole, Et Al.

Open Access Publications

No abstract provided.

Termini Restraining Of Small Membrane Proteins Enables Structure Determination At Near-Atomic Resolution, Shixuan Liu, Shuang Li, Yihu Yang, Weikai Li

Open Access Publications

Small membrane proteins are difficult targets for structural characterization. Here, we stabilize their folding by restraining their amino and carboxyl termini with associable protein entities, exemplified by the two halves of a superfolder GFP. The termini-restrained proteins are functional and show improved stability during overexpression and purification. The reassembled GFP provides a versatile scaffold for membrane protein crystallization, enables diffraction to atomic resolution, and facilitates crystal identification, phase determination, and density modification. This strategy gives rise to 14 new structures of five vertebrate proteins from distinct functional families, bringing a substantial expansion to the structural database of small membrane proteins. …

Integration Of The Drug-Gene Interaction Database (Dgidb 4.0) With Open Crowdsource Efforts, Sharon L. Freshour, Susanna Kiwala, Kelsy C. Cotto, Adam C. Coffman, Joshua F. Mcmichael, Jonathan J. Song, Malachi Griffith, Obi L. Griffith, Alex H. Wagner

Open Access Publications

The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that provides information on drug-gene interactions and druggable genes from publications, databases, and other web-based sources. Drug, gene, and interaction data are normalized and merged into conceptual groups. The information contained in this resource is available to users through a straightforward search interface, an application programming interface (API), and TSV data downloads. DGIdb 4.0 is the latest major version release of this database. A primary focus of this update was integration with crowdsourced efforts, leveraging the Drug Target Commons for community-contributed interaction data, Wikidata to facilitate term normalization, and export …

Decreased Adipose Tissue Oxygenation Associates With Insulin Resistance In Individuals With Obesity, Vincenza Cifarelli, Scott C Beeman, Gordon I Smith, Jun Yoshino, Darya Morozov, Joseph W Beals, Brandon D Kayser, Jeramie D Watrous, Mohit Jain, Bruce W Patterson, Samuel Klein

Open Access Publications

BACKGROUNDData from studies conducted in rodent models have shown that decreased adipose tissue (AT) oxygenation is involved in the pathogenesis of obesity-induced insulin resistance. Here, we evaluated the potential influence of AT oxygenation on AT biology and insulin sensitivity in people.METHODSWe evaluated subcutaneous AT oxygen partial pressure (pO2); liver and whole-body insulin sensitivity; AT expression of genes and pathways involved in inflammation, fibrosis, and branched-chain amino acid (BCAA) catabolism; systemic markers of inflammation; and plasma BCAA concentrations, in 3 groups of participants that were rigorously stratified by adiposity and insulin sensitivity: metabolically healthy lean (MHL; n = 11), metabolically healthy …

Astrocyte Deletion Of Α2-Na/K Atpase Triggers Episodic Motor Paralysis In Mice Via A Metabolic Pathway, Sarah A. Smith, Xiaoying Chen, Lindsey M. Brier, Jonathan R. Bumstead, Nicholas R. Rensing, Alison E. Ringel, Haewon Shin, Anna Oldenborg, Jan R. Crowley, Annie R. Bice, Krikor Dikranian, Joseph E. Ippolito, Marcia C. Haigis, Thomas Papouin, Guoyan Zhao, Michael Wong, Joseph P. Culver, Azad Bonni

Open Access Publications

No abstract provided.

Pathophysiological Consequences Of Katp Channel Overactivity And Pharmacological Response To Glibenclamide In Skeletal Muscle Of A Murine Model Of Cantù Syndrome, Rosa Scala, Fatima Maqoud, Nicola Zizzo, Antonietta Mele, Giulia Maria Camerino, Francesco Alfredo Zito, Girolamo Ranieri, Conor Mcclenaghan, Theresa M Harter, Colin G Nichols, Domenico Tricarico

Open Access Publications

Cantù syndrome (CS) arises from mutations in

Mycena Genomes Resolve The Evolution Of Fungal Bioluminescence, Huei-Mien Ke, Rita Jui-Hsien Lu, Et Al.

Open Access Publications

No abstract provided.

Pediatric Research Priorities In Healthcare-Associated Infections And Antimicrobial Stewardship, Susan E Coffin, Stephanie Fritz, Jason Newland, Et Al

Open Access Publications

OBJECTIVE: To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.

PARTICIPANTS: The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).

METHODS: Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and …

Cholesterol 25-Hydroxylase Suppresses Sars-Cov-2 Replication By Blocking Membrane Fusion, Ruochen Zang, James Brett Case, Xiucui Ma, Maria Florencia Gomez Castro, Zhuoming Liu, Qiru Zeng, Haiyan Zhao, Juhee Son, Paul W. Rothlauf, Gaopeng Hou, Michael D. Vahey, Kartik Mani, Daved H. Fremont, Abhinav Diwan, Michael S. Diamond, Sean P.J. Whelan, Siyuan Ding, Et Al.

Open Access Publications

No abstract provided.

A 2020 View Of Tension-Based Cortical Morphogenesis, David C. Van Essen

Open Access Publications

No abstract provided.

Endothelial Cell Cd36 Deficiency Prevents Normal Angiogenesis And Vascular Repair, Lara Bou Khzam, Ni-Huiping Son, Adam E Mullick, Nada A Abumrad, Ira J Goldberg

Open Access Publications

Endothelial cells (ECs) maintain vascular integrity and mediate vascular repair and angiogenesis, by which new blood vessels are formed from pre-existing blood vessels. Hyperglycemia has been shown to increase EC angiogenic potential. However, few studies have investigated effects of fatty acids (FAs) on EC angiogenesis. Cluster of differentiation 36 (CD36) is a FA transporter expressed by ECs, but its role in EC proliferation, migration, and angiogenesis is unknown. We sought to determine if circulating FAs regulate angiogenic function in a CD36-dependent manner. CD36-dependent effects of FAs on EC proliferation and migration of mouse heart ECs (MHECs) and lung ECs (MLECs) …

Food Addiction And Psychosocial Adversity: Biological Embedding, Contextual Factors, And Public Health Implications, David A Wiss, Nicole Avena, Mark Gold

Open Access Publications

The role of stress, trauma, and adversity particularly early in life has been identified as a contributing factor in both drug and food addictions. While links between traumatic stress and substance use disorders are well documented, the pathways to food addiction and obesity are less established. This review focuses on psychosocial and neurobiological factors that may increase risk for addiction-like behaviors and ultimately increase BMI over the lifespan. Early childhood and adolescent adversity can induce long-lasting alterations in the glucocorticoid and dopamine systems that lead to increased addiction vulnerability later in life. Allostatic load, the hypothalamic-pituitary-adrenal axis, and emerging data …

A Framework For Advancing Our Understanding Of Cancer-Associated Fibroblasts, Erik Sahai, David G. Denardo, Sheila Stewart, Et Al.

Open Access Publications

No abstract provided.

Neutrophil L-Plastin Controls Ocular Paucibacteriality And Susceptibility To Keratitis, Xiaoxiao Lu, Abirami Kugadas, Kirsten Smith-Page, Jeffrey Lamb, Tiffany Lin, Yusha Ru, Sharon Celeste Morley, Raina Fichorova, Sharad K Mittal, Sunil K Chauhan, Sejiro Littleton, Daniel Saban, Mihaela Gadjeva

Open Access Publications

Why ocular mucosa is paucibacterial is unknown. Many different mechanisms have been suggested but the comprehensive experimental studies are sparse. We found that a deficiency in L-plastin (LCP1), an actin bundling protein, resulted in an ocular commensal overgrowth, characterized with increased presence of conjunctival

Immunomodulatory Roles Of Polysaccharide Capsules In The Intestine, Samantha A Hsieh, Paul M Allen

Open Access Publications

The interplay between the immune system and the microbiota in the human intestine dictates states of health vs. disease. Polysaccharide capsules are critical elements of bacteria that protect bacteria against environmental and host factors, including the host immune system. This review summarizes the mechanisms by which polysaccharide capsules from commensal and pathogenic bacteria in the gut microbiota modulate the innate and adaptive immune systems in the intestine. A deeper understanding of the roles of polysaccharide capsules in microbiota-immune interactions will provide a basis to harness their therapeutic potential to advance human health.

Pancreatic Triglyceride Lipase Mediates Lipotoxic Systemic Inflammation, Cristiane De Oliveira, Mark E Lowe, Et Al

Open Access Publications

Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show adipose involvement in abdominal diseases, their outcomes may vary from being a mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral adipose injury during acute pancreatitis and acute diverticulitis to determine its role in organ failure. Acute pancreatitis-associated adipose tissue had ongoing lipolysis in the absence of adipocyte triglyceride lipase (ATGL). Pancreatic lipase injected into mouse visceral adipose tissue hydrolyzed adipose triglyceride and generated excess nonesterified fatty acids (NEFAs), which caused organ failure in the absence …

Lipin-1 Contributes To Il-4 Mediated Macrophage Polarization, Sunitha Chandran, Robert M Schilke, Cassidy M R Blackburn, Aila Yurochko, Rusella Mirza, Rona S Scott, Brian N Finck, Matthew D Woolard

Open Access Publications

Macrophage responses contribute to a diverse array of pathologies ranging from infectious disease to sterile inflammation. Polarization of macrophages determines their cellular function within biological processes. Lipin-1 is a phosphatidic acid phosphatase in which its enzymatic activity contributes to macrophage pro-inflammatory responses. Lipin-1 also possesses transcriptional co-regulator activity and whether this activity is required for macrophage polarization is unknown. Using mice that lack only lipin-1 enzymatic activity or both enzymatic and transcriptional coregulator activities from myeloid cells, we investigated the contribution of lipin-1 transcriptional co-regulator function toward macrophage wound healing polarization. Macrophages lacking both lipin-1 activities did not elicit IL-4 …

Gardnerella Vaginalis As A Cause Of Bacterial Vaginosis: Appraisal Of The Evidence From In Vivo Models, Sydney Morrill, Nicole M Gilbert, Amanda L Lewis

Open Access Publications

Koch's postulates dictate the use of experimental models to illustrate features of human disease and provide evidence for a singular organism as the cause. The underlying cause(s) of bacterial vaginosis (BV) has been debated in the literature for over half a century. In 1955, it was first reported that a bacterium now known as

Co-Occurrence Of Campylobacter Species In Children From Eastern Ethiopia, And Their Association With Environmental Enteric Dysfunction, Diarrhea, And Host Microbiome, Yitagele Terefe, Mark J Manary, Maria Isabel Ordiz, Et Al

Open Access Publications

High

Multiple Network Disconnection In Anosognosia For Hemiplegia, Elena Monai, Francesca Bernocchi, Marta Bisio, Antonio Luigi Bisogno, Alessandro Salvalaggio, Maurizio Corbetta

Open Access Publications

Anosognosia for hemiplegia (AHP) is a complex syndrome whose neural correlates are still under investigation. One hypothesis, mainly based on lesion mapping studies, is that AHP reflects a breakdown of neural systems of the right hemisphere involved in motor function. However, more recent theories have suggested that AHP may represent a disorder of cognitive systems involved in belief updating, self-referential or body processing. Two recent studies, using a method to estimate the degree of white matter disconnection from lesions, have indeed shown that patients with AHP suffer from damage of several long-range white matter pathways in association cortex. Here, we …

Development Of Volumetric Independent Dose Calculation System For Verification Of The Treatment Plan In Image-Guided Adaptive Brachytherapy, Sang-Won Kang, Jin-Beom Chung, Kyeong-Hyeon Kim, Ji-Yeon Park, Hae-Jin Park, Woong Cho, Sven Olberg, Tae Suk Suh, Justin C Park

Open Access Publications

No abstract provided.

Sequencing-Based Measurable Residual Disease Testing In Acute Myeloid Leukemia, Jennifer M Yoest, Cara Lunn Shirai, Eric J Duncavage

Open Access Publications

Next generation sequencing (NGS) methods have allowed for unprecedented genomic characterization of acute myeloid leukemia (AML) over the last several years. Further advances in NGS-based methods including error correction using unique molecular identifiers (UMIs) have more recently enabled the use of NGS-based measurable residual disease (MRD) detection. This review focuses on the use of NGS-based MRD detection in AML, including basic methodologies and clinical applications.

Dopamine Buffering Capacity Imaging: A Pharmacodynamic Fmri Method For Staging Parkinson Disease, Kevin J Black, Haley K Acevedo, Jonathan M Koller

Open Access Publications

We propose a novel pharmacological fMRI (phMRI) method for objectively quantifying disease severity in Parkinson disease (PD). It is based on the clinical observation that the benefit from a dose of levodopa wears off more quickly as PD progresses. Biologically this has been thought to represent decreased buffering capacity for dopamine as nigrostriatal cells die. Buffering capacity has been modeled based on clinical effects, but clinical measurements are influenced by confounding factors. The new method proposes to measure the effect objectively based on the timing of the known response of several brain regions to exogenous levodopa. Such responses are robust …

Positive Allosteric Modulation Of Cd11b As A Novel Therapeutic Strategy Against Lung Cancer, Terese Geraghty, Anugraha Rajagopalan, Rabail Aslam, Alexander Pohlman, Ishwarya Venkatesh, Andrew Zloza, David Cimbaluk, David G Denardo, Vineet Gupta

Open Access Publications

Lung cancer is one of the leading causes of cancer-related deaths in the United States. A major hurdle for improved therapies is immune suppression mediated by the tumor and its microenvironment. The lung tumor microenvironment (TME) contains large numbers of tumor-associated macrophages (TAMs), which suppress the adaptive immune response, increase neo-vascularization of the tumor, and provide pro-tumor factors to promote tumor growth. CD11b is highly expressed on myeloid cells, including TAMs, where it forms a heterodimeric integrin receptor with CD18 (known as CD11b/CD18, Mac-1, CR3, and αMβ2), and plays an important role in recruitment and biological functions of these cells, …

Methylation-Directed Glycosylation Of Chromatin Factors Represses Retrotransposon Promoters, Mathieu Boulard, Sofia Rucli, John R. Edwards, Timothy H. Bestor

Open Access Publications

No abstract provided.

The Role Of Ct-Quantified Body Composition On Longitudinal Health-Related Quality Of Life In Colorectal Cancer Patients: The Colocare Study, Biljana Gigic, Graham A Colditz, Adetunji T Toriola, Et Al

Open Access Publications

BACKGROUND: Obesity, defined by body mass index (BMI), measured at colorectal cancer (CRC) diagnosis has been associated with postoperative complications and survival outcomes. However, BMI does not allow for a differentiation between fat and muscle mass. Computed tomography (CT)-defined body composition more accurately reflects different types of tissue and their associations with health-related quality of life (HRQoL) during the first year of disease, but this has not been investigated yet. We studied the role of visceral and subcutaneous fat area (VFA and SFA) and skeletal muscle mass (SMM) on longitudinally assessed HRQoL in CRC patients.

METHODS: A total of 138 …